Diagnostic accuracy of the re-engineered urinary FujiLAM2 assay amongst hospitalized adults with advanced HIV disease: a prospective cohort study

Background: A non-sputum based, point-of-care TB diagnostic test is a global health priority. The impact of urinary mycobacterial lipoarabinomannan (LAM) testing has been limited by the diagnostic performance of current assays. We assessed the diagnostic accuracy of the re-engineered TB-LAM SILVAMP (FujjLAM2) assay (Fujifilm, Japan) to diagnose TB amongst hospitalised adults living with advanced HIV disease. Methods: We consecutively enrolled adults presenting with suspected meningitis at two hospitals in Uganda. We implemented a standardised TB diagnostic package: 1) urine Alere TB lipoarabinomannan (TB-LAM), 2) urine Xpert MTB/Rif Ultra, 3) CSF Xpert MTB/Rif Ultra, 4) TB CSF culture, 5) mycobacterial blood culture, 6) chest radiography. We performed FujiLAM2 testing on cryopreserved or fresh urine. We compared diagnostic accuracy against a composite microbiological reference standard of any positive TB test (including Alere-LAM). We assessed 30-day mortality. Findings: We performed FujiLAM2 testing on urine of 436 hospitalised participants. The median CD4 count was 34-cells/mcL (IQR, 11-96). Using the microbiologic reference standard, FujiLAM2 sensitivity was 34% (95%CI, 25-43%), and specificity was 94% (95%CI, 91-96%). When grade-1 Alere TB-LAM positives were excluded, sensitivity was 38% (95%CI, 27-50%). Cryopreserved specimens were 3-fold more frequently positive. Interpretation: Amongst hospitalised adults with advanced HIV disease, the re-engineered FujiLAM2 urine assay had suboptimal sensitivity but high specificity for diagnosing TB disease. Antigen-antibody/protein complexes may be present accounting for better sensitivity with cryopreserved specimens. Funding: National Institute of Neurologic Disorders and Stroke, National Institute of Allergy and Infectious Diseases, Wellcome Trust.